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FARA Funded Research

Your generous support has funded all the research listed below.


For more information on FARA-funded research & scientists, please visit FARA Supported Research, Active Clinical Trials and the Featured Scientist.

Therapeutic Prospects for Friedreich's Ataxia

Friedreich's ataxia (FRDA) is a progressive disease affecting multiple organs that is caused by systemic insufficiency of the mitochondrial protein frataxin. Current therapeutic strategies aim to elevate frataxin levels and/or alleviate the consequences of frataxin deficiency. Recent significant advances in the FRDA therapeutic pipeline are bringing patients closer to a cure.

Read the entire article HERE

The Role of Iron in Friedreich's Ataxia: Insights From Studies in Human Tissues and Cellular and Animal Models

Friedreich's ataxia (FA) is a rare early-onset degenerative disease that affects both the central and peripheral nervous systems, and other tissues, mainly the heart and pancreas. This disorder progresses as a mixed sensory and cerebellar ataxia, primarily disturbing the proprioceptive pathways in the spinal cord, peripheral nerves and nuclei of the cerebellum. FA is an inherited disease caused by an insufficient amount of the nuclear-encoded mitochondrial protein frataxin, which is an essential and highly evolutionary conserved protein whose deficit results in iron metabolism dysregulation and mitochondrial dysfunction. The first experimental evidence connecting frataxin with iron homeostasis came from yeast; iron accumulates in the mitochondria of yeast with deletion of the frataxin equivalent gene. This finding was soon linked to previous observations of iron deposits in the hearts of FA patients and was later reported in animal models of the disease. Despite advances made in the understanding of FA pathophysiology, the role of iron in this disease has not yet been completely clarified. Some of the questions still unresolved include the molecular mechanisms responsible for the iron accumulation and iron-mediated toxicity. Here, we review the contribution of the cellular and animal models of FA and relevance of the studies using FA patient samples to gain knowledge about these issues. Mechanisms of mitochondrial iron overload are discussed considering the potential roles of frataxin in the major mitochondrial metabolic pathways that use iron. We also analyzed the effect of iron toxicity on neuronal degeneration in FA by reactive oxygen species (ROS)-dependent and ROS-independent mechanisms. Finally, therapeutic strategies based on the control of iron toxicity are considered.

Read the entire article HERE

Progress in understanding Friedreich's ataxia using human induced pluripotent stem cells

Neuronal and cardiac cells are primary targets of frataxin deficiency and generating models via differentiation of induced pluripotent stem cells (iPSCs) into these cell types is essential for progress towards developing therapies for FA. This review is focused on modeling FA using human iPSCs and various iPSC-differentiated cell types. The authors emphasize the importance of patient and corrected isogenic cell line pairs to minimize effects caused by biological variability between individuals.

The versatility of iPSC-derived cellular models of FA is advantageous for developing new therapeutic strategies, and rigorous testing in such models will be critical for approval of the first treatment for FA. Creating a well-characterized and diverse set of iPSC lines, including appropriate isogenic controls, will facilitate achieving this goal. Also, improvement of differentiation protocols, especially towards proprioceptive sensory neurons and organoid generation, is necessary to utilize the full potential of iPSC technology in the drug discovery process.

Read the entire article HERE

C-Path and FARA announce the launch of the FA Integrated Clinical Database

Critical Path Institute's (C-Path) Data Collaboration Center (DCC) and the Friedreich's Ataxia Research Alliance (FARA) today announced the launch of the Friedreich's Ataxia Integrated Clinical Database (FAICD). The new platform will enable collaborative research and data sharing to support the understanding of natural history, potential biomarkers and clinical endpoints, and promote research into novel clinical trial design in Friedreich's ataxia (FA). By making this data available to researchers, the organizations hope to enable the development of tools that will help design and interpret efficient clinical trials — leading to effective treatments for FA as soon as possible.

Read the entire Press Release HERE

Ferroptosis as a novel therapeutic target for Friedreich's ataxia

Friedreich ataxia (FRDA) is a progressive neuro- and cardio-degenerative disorder characterized by ataxia, sensory loss, and hypertrophic cardiomyopathy. In most cases, the disorder is caused by GAA repeat expansions in the first introns of both alleles of the FXN gene, resulting in decreased expression of the encoded protein, frataxin. Frataxin localizes to the mitochondrial matrix and is required for iron-sulfur-cluster biosynthesis. Decreased expression of frataxin is associated with mitochondrial dysfunction, mitochondrial iron accumulation, and increased oxidative stress. Ferropotosis is a recently identified pathway of regulated, iron-dependent cell death, which is biochemically distinct from apoptosis. This group evaluated whether there is evidence for ferroptotic pathway activation in cellular models of FRDA. They found that primary patient-derived fibroblasts, murine fibroblasts with FRDA-associated mutations, and murine fibroblasts in which a repeat expansion had been introduced (KIKO) were more sensitive than normal control cells to erastin, a known ferroptosis inducer. We also found that the ferroptosis inhibitors SRS11-92 and Fer-1, used at 500 nM, were efficacious in protecting human and mouse cellular models of FRDA treated with ferric ammonium citrate (FAC) and an inhibitor of glutathione synthesis (BSO), whereas caspase-3 inhibitors failed to show significant biological activity. Cells treated with FAC and BSO consistently showed decreased glutathione-dependent peroxidase activity and increased lipid peroxidation, both hallmarks of ferroptosis. Finally, the ferroptosis inhibitor SRS11-92 decreased the cell death associated with frataxin knockdown in healthy human fibroblasts. Taken together, these data suggest that ferroptosis inhibitors may have therapeutic potential in FRDA.

Read the entire article HERE

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